7-129648270-T-C

Variant names:

• chr7-129648270-T-C
• rs11487138
• NM_005011.5:c.-6-9076T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005011.5(NRF1):​c.-6-9076T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 147,118 control chromosomes in the GnomAD database, including 2,712 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2712 hom., cov: 29)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 2 publications found

Genes affected

NRF1 (HGNC:7996): (nuclear respiratory factor 1) This gene encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternative splicing results in multiple transcript variants. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005011.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	NM_005011.5	MANE Select	c.-6-9076T>C		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.-9-9073T>C		intron	N/A	NP_001280092.1
	NRF1	NM_001040110.2		c.-9-9073T>C		intron	N/A	NP_001035199.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	ENST00000393232.6	TSL:1 MANE Select	c.-6-9076T>C		intron	N/A	ENSP00000376924.1
	NRF1	ENST00000311967.6	TSL:1	c.-9-9073T>C		intron	N/A	ENSP00000309826.2
	NRF1	ENST00000393230.6	TSL:1	c.-9-9073T>C		intron	N/A	ENSP00000376922.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 26575 AN: 147044 Hom.: 2702 Cov.: 29

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 26586 AN: 147118 Hom.: 2712 Cov.: 29 AF XY: 0.182 AC XY: 12970 AN XY: 71232

African (AFR) AF: 0.162 AC: 6427 AN: 39682

American (AMR) AF: 0.201 AC: 2896 AN: 14396

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 376 AN: 3460

East Asian (EAS) AF: 0.465 AC: 2290 AN: 4930

South Asian (SAS) AF: 0.295 AC: 1390 AN: 4716

European-Finnish (FIN) AF: 0.150 AC: 1374 AN: 9150

Middle Eastern (MID) AF: 0.138 AC: 39 AN: 282

European-Non Finnish (NFE) AF: 0.168 AC: 11344 AN: 67550

Other (OTH) AF: 0.162 AC: 332 AN: 2044

Alfa AF: 0.176 Hom.: 310

Bravo AF: 0.188

Asia WGS AF: 0.364 AC: 1260 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.81
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11487138; hg19: chr7-129288110;